The immunodisturbances caused by the human immunodeficiency virus have been studied, but the nature of the progress of the disease is still uncertain. However, it has been shown that HIV-infected humans have circulating cytotoxic T-lymphocytes that lyse uninfected CD4+ cells. Zarling et al., J. Immunol., 144:2992 (1990). It is also generally understood that infection with HIV, while depleting the levels of CD4+ cells, enhances the levels of CD8+, DR+, and IL-2R+ leukocytes. IL-2R+ is considered an activation marker, and DR+ is an HLA marker. These may be present on cells with additional markers such as CD4+ and CD8+.
One approach to interfering with the progress of this infection, and the resultant immunosuppression, employs strategies to alter the composition of the blood with respect to various components of the immune system. In one attempt to achieve this, U.S. Pat. No. 4,960,408 discloses a process of treating a subject having AIDS-related complex systemically with psoralen, and then extracorporeally treating the T-lymphocytes with ultraviolet radiation having a wavelength absorbed by the psoralen compound. The irradiated T-cells are then returned to the subject. This treatment apparently enhances the levels of CD3+, CD4+, and CD8+ cells, although not in a uniform fashion.
Photodynamic therapy generally involves the administration of a photoactive agent, permitting the agent to home to cells or tissues whose destruction is sought, and irradiating the cell or tissue with light absorbed by the photoactive agent. In theory, the excited photoactive agent, in decaying to its ground state, generates substances, putatively singlet oxygen, which are toxic to the proximal cells or tissues.
Photodynamic therapy was initially applied to the treatment of tumors in humans and animals. A number of classes of photoactive agents have been described, including psoralens, which are activated by UV light, various hematoporphyrin derivatives which are activated by visible light, and other aromatic systems such as phthalocyanines and modified porphyrins such as chlorins. In addition, U.S. Pat. No. 5,095,030, issued 10 Mar. 1992, which is incorporated herein by reference in its entirety, discloses and claims various wavelength-specific cytotoxic agents that are generically described as “green porphyrins.” These compounds are porphyrin derivatives that are modified by a Diels Alder reaction to shift the wavelength of absorption effectively to a longer wavelength. This results in some favorable properties as compared with, for example, hematoporphyrin derivative, when these compounds are employed in photodynamic therapy generally. As described in this patent, these cytotoxic agents, generally called BPDs, absorb visible light at wavelengths which minimize interference by surrounding tissue with the incoming irradiation.
In addition to treatment of tumors and malignancies, photodynamic therapy has been suggested for disrupting atherosclerotic plaques, and for ridding blood supplies of pathogenic agents. In general it was considered that the photoactive agent would be selectively attracted to or retained in the unwanted cells or tissue, as compared to normal cells or tissue and the selectivity of the protocol has been based partly on this feature of the photoactive agents and partly on the focusing of the location at which the visible or UV light is applied.
It has now been found possible to diminish selectively the levels of activated leukocyte subsets that are associated with HIV infection or other immune dysfunctions using a photoactive agent, particularly the green porphyrin compounds described above. This depletion can be effected without side effects on the normally functioning B cell, CD4+ cell, CD8+ cell or NK cell populations. Either leukocytes after separation from red blood cells or whole blood can be treated using the method of the invention.
It has now also been found that two specific autoimmune diseases, multiple sclerosis and rheumatoid arthritis, are verified to respond to photodynamic therapy, not only with respect to use of green porphyrins as photoactive agents, but utilizing photodynamic therapeutic agents generally as well.